Chelikani Prasanth K, Haver Alvin C, Reidelberger Roger D
Department of Veterans Affairs Nebraska Western Iowa Health Care System, Omaha, NE 68105, USA.
Am J Physiol Regul Integr Comp Physiol. 2005 Jun;288(6):R1695-706. doi: 10.1152/ajpregu.00870.2004. Epub 2005 Feb 17.
Glucagon-like peptide-1(7-36)-amide (GLP-1) is postulated to act as a hormonal signal from gut to brain to inhibit food intake and gastric emptying. A mixed-nutrient meal produces a 2 to 3-h increase in plasma GLP-1. We determined the effects of intravenous infusions of GLP-1 on food intake, sham feeding, and gastric emptying in rats to assess whether GLP-1 inhibits food intake, in part, by slowing gastric emptying. A 3-h intravenous infusion of GLP-1 (0.5-170 pmol.kg(-1).min(-1)) at dark onset dose-dependently inhibited food intake in rats that were normally fed with a potency (mean effective dose) and efficacy (maximal % inhibition) of 23 pmol.kg(-1).min(-1) and 82%, respectively. Similar total doses of GLP-1 administered over a 15-min period were less potent and effective. In gastric emptying experiments, GLP-1 (1.7-50 pmol.kg(-1).min(-1)) dose-dependently inhibited gastric emptying of saline and ingested chow with potencies of 18 and 6 pmol.kg(-1).min(-1) and maximal inhibitions of 74 and 83%, respectively. In sham-feeding experiments, GLP-1 (5-50 pmol.kg(-1).min(-1)) dose-dependently reduced 15% aqueous sucrose intake in a similar manner when gastric cannulas were closed (real feeding) and open (sham feeding). These results demonstrate that intravenous infusions of GLP-1 dose-dependently inhibit food intake, sham feeding, and gastric emptying with a similar potency and efficacy. Thus GLP-1 may inhibit food intake in part by reducing gastric emptying, yet can also inhibit food intake independently of its action to reduce gastric emptying. It remains to be determined whether intravenous doses of GLP-1 that reproduce postprandial increases in plasma GLP-1 are sufficient to inhibit food intake and gastric emptying.
胰高血糖素样肽-1(7-36)-酰胺（GLP-1）被认为是一种从肠道传递至大脑的激素信号，可抑制食物摄入和胃排空。混合营养餐会使血浆GLP-1水平升高2至3小时。我们通过静脉输注GLP-1来测定其对大鼠食物摄入、假饲和胃排空的影响，以评估GLP-1是否部分通过减缓胃排空来抑制食物摄入。在黑暗开始时进行3小时的GLP-1静脉输注（0.5 - 170 pmol·kg⁻¹·min⁻¹），剂量依赖性地抑制正常进食大鼠的食物摄入，其效力（平均有效剂量）和效能（最大抑制百分比）分别为23 pmol·kg⁻¹·min⁻¹和82%。在15分钟内给予相似总剂量的GLP-1，其效力和效果则较弱。在胃排空实验中，GLP-1（1.7 - 50 pmol·kg⁻¹·min⁻¹）剂量依赖性地抑制生理盐水和摄入食物的胃排空，效力分别为18和6 pmol·kg⁻¹·min⁻¹，最大抑制率分别为74%和83%。在假饲实验中当胃插管关闭（实际进食）和打开（假饲）时，GLP-1（5 - 50 pmol·kg⁻¹·min⁻¹）以相似的方式剂量依赖性地减少15%的蔗糖水溶液摄入量。这些结果表明，静脉输注GLP-1剂量依赖性地抑制食物摄入、假饲和胃排空，且效力和效能相似。因此，GLP-1可能部分通过减少胃排空来抑制食物摄入，但也可独立于其减少胃排空的作用来抑制食物摄入。静脉注射能重现餐后血浆GLP-1升高的剂量是否足以抑制食物摄入和胃排空仍有待确定。
